Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours

Avishai Gavish, Michael Tyler, Alissa C. Greenwald, Rouven Hoefflin, Dor Simkin, Roi Tschernichovsky, Noam Galili Darnell, Einav Somech, Chaya Barbolin, Tomer Antman, Daniel Kovarsky, Thomas Barrett, L. Nicolas Gonzalez Castro, Debdatta Halder, Rony Chanoch-Myers, Julie Laffy, Michael Mints, Adi Wider, Rotem Tal, Avishay Spitzer, Toshiro Hara, Maria Raitses-Gurevich, Chani Stossel, Talia Golan, Amit Tirosh, Mario L. Suvà, Sidharth V. Puram and Itay Tirosh ()
Additional contact information
Avishai Gavish: Weizmann Institute of Science
Michael Tyler: Weizmann Institute of Science
Alissa C. Greenwald: Weizmann Institute of Science
Rouven Hoefflin: Weizmann Institute of Science
Dor Simkin: Weizmann Institute of Science
Roi Tschernichovsky: Weizmann Institute of Science
Noam Galili Darnell: Weizmann Institute of Science
Einav Somech: Weizmann Institute of Science
Chaya Barbolin: Weizmann Institute of Science
Tomer Antman: Weizmann Institute of Science
Daniel Kovarsky: Weizmann Institute of Science
Thomas Barrett: Washington University School of Medicine
L. Nicolas Gonzalez Castro: Massachusetts General Hospital and Harvard Medical School
Debdatta Halder: Weizmann Institute of Science
Rony Chanoch-Myers: Weizmann Institute of Science
Julie Laffy: Weizmann Institute of Science
Michael Mints: Weizmann Institute of Science
Adi Wider: Weizmann Institute of Science
Rotem Tal: Weizmann Institute of Science
Avishay Spitzer: Weizmann Institute of Science
Toshiro Hara: Massachusetts General Hospital and Harvard Medical School
Maria Raitses-Gurevich: The Oncology Institute, Chaim Sheba Medical Center
Chani Stossel: The Oncology Institute, Chaim Sheba Medical Center
Talia Golan: The Oncology Institute, Chaim Sheba Medical Center
Amit Tirosh: Tel Aviv University
Mario L. Suvà: Massachusetts General Hospital and Harvard Medical School
Sidharth V. Puram: Washington University School of Medicine
Itay Tirosh: Weizmann Institute of Science

Nature, 2023, vol. 618, issue 7965, 598-606

Abstract: Abstract Each tumour contains diverse cellular states that underlie intratumour heterogeneity (ITH), a central challenge of cancer therapeutics1. Dozens of recent studies have begun to describe ITH by single-cell RNA sequencing, but each study typically profiled only a small number of tumours and provided a narrow view of transcriptional ITH2. Here we curate, annotate and integrate the data from 77 different studies to reveal the patterns of transcriptional ITH across 1,163 tumour samples covering 24 tumour types. Among the malignant cells, we identify 41 consensus meta-programs, each consisting of dozens of genes that are coordinately upregulated in subpopulations of cells within many tumours. The meta-programs cover diverse cellular processes including both generic (for example, cell cycle and stress) and lineage-specific patterns that we map into 11 hallmarks of transcriptional ITH. Most meta-programs of carcinoma cells are similar to those identified in non-malignant epithelial cells, suggesting that a large fraction of malignant ITH programs are variable even before oncogenesis, reflecting the biology of their cell of origin. We further extended the meta-program analysis to six common non-malignant cell types and utilize these to map cell–cell interactions within the tumour microenvironment. In summary, we have assembled a comprehensive pan-cancer single-cell RNA-sequencing dataset, which is available through the Curated Cancer Cell Atlas website, and leveraged this dataset to carry out a systematic characterization of transcriptional ITH.

Date: 2023
References: Add references at CitEc
Citations: View citations in EconPapers (7)

Downloads: (external link)
https://www.nature.com/articles/s41586-023-06130-4 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:618:y:2023:i:7965:d:10.1038_s41586-023-06130-4

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-023-06130-4

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().